Variants of Uncertain Significance (VUS) are limiting the success of targeted therapies

Cancer research has established that tumorigenesis and tumor progression typically result from the accumulation of somatic genomic alterations over the life span of the tumor. Alterations that are integral to a tumor’s growth and survival are known as driver mutations; the others are known as passenger mutations. Mutations that are not yet characterized, VUS, may turn out to be driver mutations and, as such, may be translated to proteins that dysregulate signaling pathways (for example, actively promoting excessive replication, or inhibiting apoptosis).

Monitor the activity levels of the signaling pathways, analyze response to targeted therapies.

NGS reveals mutations, but provides no knowledge of whether the translated protein is actually aberrantly activated. This is because the functional significance of most mutations is uncertain, let alone that of networks of interacting proteins. NovellusDx monitors the activity level of signaling pathways that results from found mutations and tests how the activity responds to targeted therapies.

Once we receive the NGS data, we resynthesize the genes with all the mutations - driver, passenger and VUS - and express them in a cell-line. After an incubation period, the cells are scanned in a high-content microscopy system and analyzed using our proprietary algorithms to determine the localization of specific downstream reporters inside the cells. This tells us the activity level of each signaling pathway. We then repeat the process with the incubation of targeted therapies which allows us to assess drug response.

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Our lab is both CMS and CLIA certified. In November 2015, the lab received ISO 13485:2003 for the “development of diagnostic solutions for personalized medicine”. This allows us to serve patients from the US and internationally.